Gastric cancer (herein also referred to as “GC”) is the fourth most common cancer in the world and the second leading cause of cancer mortality. In Western countries the expected 5-year survival rate at diagnosis is only 10-30%. This can be attributed to a paucity of diagnostic symptoms and subsequent endoscopic diagnosis at advanced stage. Unfortunately, when symptoms of GC present themselves metastasis has already occurred in >80% of cases.
Japan has one of the world's highest rates of GC. The implementation of a mass screening program of asymptomatic individuals by gastric photofluorography in Japan has increased the number of GC cases detected at the early-stage, improving the overall 5-year survival rate to more than 50%. The sensitivity and specificity of gastric photofluorography are good at 70-90% and 80-90%, respectively. However, cost-effectiveness studies have indicated that a gastric photofluorography program is not viable in Western countries where the incidence of GC is lower. A more suitable diagnostic approach would involve an accurate, non-invasive and cost-effective test for the detection of GC biomarkers involved in GC aetiology.
The existing clinical markers used in GC, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA 72-4, are neither sufficiently sensitive nor specific for routine screening and are primarily used to monitor the progression of disease following treatment. The serum ratio of pepsinogen I/II has shown some promise as an alternative GC indicator in Asian populations, however, questions remain regarding its applicability in other racial groups including Western populations.
There are several profound obstacles associated with biomarker discovery for GC. Obtaining human samples of early-stage disease is difficult given its asymptomatic nature. The problem is further compounded by the genetic diversity of human populations and the influence of uncontrollable environmental factors meaning that potential biomarkers can be overshadowed by the high degree of natural variation in biomarker expression.
These aforementioned difficulties have led to a paucity of sensitive and specific biomarkers indicative of GC. Accordingly, the identification of new biomarkers suitable for detecting early-stage GC in a large population is urgently required.
Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in any country.